Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?

Autores
Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; Carrillo, Maria Cristina
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.
Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Materia
Beta-Catenin
Transforming Growth Factor Beta-1
Interferon-Alfa
Smad Proteins
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15408
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15408
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?Ceballos, Maria PaulaParody, Juan PabloAlvarez, María de LujánIngaramo, Paola InésCarnovale, Cristina EsterCarrillo, Maria CristinaBeta-CateninTransforming Growth Factor Beta-1Interferon-AlfaSmad Proteinshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaElsevier Inc2011-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15408Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-16910006-2952enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2011.08.001info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006295211006435info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:30:41Zoai:ri.conicet.gov.ar:11336/15408instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:30:41.75CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
title Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
spellingShingle Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
Ceballos, Maria Paula
Beta-Catenin
Transforming Growth Factor Beta-1
Interferon-Alfa
Smad Proteins
title_short Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
title_full Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
title_fullStr Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
title_full_unstemmed Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
title_sort Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?
dc.creator.none.fl_str_mv Ceballos, Maria Paula
Parody, Juan Pablo
Alvarez, María de Luján
Ingaramo, Paola Inés
Carnovale, Cristina Ester
Carrillo, Maria Cristina
author Ceballos, Maria Paula
author_facet Ceballos, Maria Paula
Parody, Juan Pablo
Alvarez, María de Luján
Ingaramo, Paola Inés
Carnovale, Cristina Ester
Carrillo, Maria Cristina
author_role author
author2 Parody, Juan Pablo
Alvarez, María de Luján
Ingaramo, Paola Inés
Carnovale, Cristina Ester
Carrillo, Maria Cristina
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Beta-Catenin
Transforming Growth Factor Beta-1
Interferon-Alfa
Smad Proteins
topic Beta-Catenin
Transforming Growth Factor Beta-1
Interferon-Alfa
Smad Proteins
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.
Fil: Ceballos, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Parody, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Alvarez, María de Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
Fil: Carrillo, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina
description Wnt/b-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated b-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-a (IFN-a) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-b1 (TGF-b1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/b-catenin and TGF-b1/Smads pathways is the association of Smads with b-catenin/TCF4. In this study we analyzed the effects of IFNa2b and TGF-b1 treatments on Wnt/b-catenin pathway, Smads proteins levels, b-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-a2b and TGFb1 attenuated Wnt/b-catenin signal by decreasing b-catenin and Frizzled7 receptor proteins contents and the interaction of b-catenin with TCF4. Truncated b-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates b-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-a2b and TGF-b1 proved to be effective as modulators of Wnt/b-catenin pathway in HCC cell lines holding both wild-type and truncated b-catenin. Since the inhibition ofb-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-a2b and TGF-b1 could be useful as potential treatments in patients with HCC.
publishDate 2011
dc.date.none.fl_str_mv 2011-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15408
Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-1691
0006-2952
url http://hdl.handle.net/11336/15408
identifier_str_mv Ceballos, Maria Paula; Parody, Juan Pablo; Alvarez, María de Luján; Ingaramo, Paola Inés; Carnovale, Cristina Ester; et al.; Interferon-a2b and transforming growth factor-b1 treatments on HCC cell lines: are Wnt/b-catenin pathway and Smads signaling connected in hepatocellular carcinoma?; Elsevier Inc; Biochemical Pharmacology; 82; 11; 12-2011; 1682-1691
0006-2952
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcp.2011.08.001
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006295211006435
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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